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Leflunomide Versus Sulfasalazine/Methotrexate in Rheumatoid Arthritis:an Ultrasound/Magnetic Resonance Imaging Study

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ClinicalTrials.gov Identifier: NCT01659242
Recruitment Status : Terminated
First Posted : August 7, 2012
Last Update Posted : December 2, 2014
Sponsor:
Information provided by (Responsible Party):
Singapore General Hospital

Tracking Information
First Submitted Date  ICMJE August 3, 2012
First Posted Date  ICMJE August 7, 2012
Last Update Posted Date December 2, 2014
Study Start Date  ICMJE July 2012
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2012)
MRI synovitis score [ Time Frame: four months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01659242 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2012)
  • MRI bone marrow edema score [ Time Frame: 4 months ]
  • MRI erosion score [ Time Frame: 4 months ]
  • US synovitis score [ Time Frame: 4 months ]
  • clinical outcomes [ Time Frame: 4 months ]
    Swollen/Tender joint counts, investigator's global assessment of disease activity (0-10), patient's assessment of disease activity (0-10), pain assessment by visual analogue scale (0-10), erythrocyte sedimentation rate, duration (mins) of early morning stiffness, and calculated disease activity indices
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 6, 2012)
  • US erosion score [ Time Frame: 4 months ]
  • US tenosynovitis score [ Time Frame: 4 months ]
  • MRI tenosynovitis score [ Time Frame: 4 months ]
  • Adverse events [ Time Frame: 4 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Leflunomide Versus Sulfasalazine/Methotrexate in Rheumatoid Arthritis:an Ultrasound/Magnetic Resonance Imaging Study
Official Title  ICMJE Leflunomide Versus Sulfasalazine/Methotrexate in Rheumatoid Arthritis Patients With Active Disease Despite Methotrexate: an Ultrasound and Magnetic Resonance Imaging Study
Brief Summary In rheumatoid arthritis patients with active disease despite optimal treatment with methotrexate, the main objective of this pilot study is to use advance imaging tools such as magnetic resonance imaging and ultrasound to evaluate which treatment option is more efficacious: initiating methotrexate/sulfasalazine combination therapy, or switching to leflunomide monotherapy
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Methotrexate plus sulfasalazine

    ARM 1(Methotrexate(MTX) plus Sulfasalazine(SSZ))

    SSZ:Oral form, 2g/day, with escalation regime starting from 1g/day for the first week and increase to 1.5g/day in the next week and increasing to 2g/day by the third week. Total treatment period is 16 weeks. After reaching 2g/day, if patients conditions warrants (and no contraindication), SSZ may be increased at 0.5g per clinic visit) up to a maximum of 3g/day.

    MTX:Kept at the highest optimal dose.

    Other Name: n.a
  • Drug: Leflunomide

    ARM 2:Leflunomide(LEF)

    LEF: Oral form, 20mg every other day for first 2 weeks then increasing to 20mg per day by the third week. Total treatment period is 16 weeks.

    Methotrexate:Off

    Other Name: n.a
Study Arms  ICMJE
  • Active Comparator: Methotrexate plus sulfasalazine

    ARM 1(Methotrexate(MTX) plus Sulfasalazine(SSZ))

    SSZ:Oral form, 2g/day, with escalation regime starting from 1g/day for the first week and increase to 1.5g/day in the next week and increasing to 2g/day by the third week. Total treatment period is 16 weeks. After reaching 2g/day, if patients conditions warrants (and no contraindication), SSZ may be increased at 0.5g per clinic visit) up to a maximum of 3g/day.

    MTX:Kept at the highest optimal dose.

    Intervention: Drug: Methotrexate plus sulfasalazine
  • Active Comparator: Leflunomide

    ARM 2:Leflunomide(LEF)

    LEF: Oral form, 20mg every other day for first 2 weeks then increasing to 20mg per day by the third week. Total treatment period is 16 weeks.

    Methotrexate:Off

    Intervention: Drug: Leflunomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 26, 2014)
1
Original Estimated Enrollment  ICMJE
 (submitted: August 6, 2012)
20
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Male and female patients aged between 21 and 65 years.
  2. Patients with no childbearing potential (For example postmenopausal or sterilised) or have decided not to have offspring(s).
  3. All female patients must consent not to get pregnant/breastfeed, male patients must consent not to father a child and all must consent to practice effective birth control.
  4. Fulfills either the 1987 ACR criteria and/or the 2010 ACR / EULAR RA Classification Criteria.
  5. Seropositivity: Rheumatoid factor (RF) and/or anti -cyclic citrullinated protein antibodies (anti-CCP) must be positive.
  6. MCPJ(s) and/or Wrist(s) joint(s) involvement.
  7. Rheumatoid arthritis patients (less than 5 years duration) who remain at least moderately active based on DAS28 score of > 3.2, following 3 months of therapy with an optimal dose of methotrexate(e.g. at least 15 mg/week).
  8. If patient is on oral corticosteroids, this should not exceeding 10mg prednisolone daily (or oral steroid equivalent) for at least 4 weeks and should be at an unchanged dose for at least 2 weeks before entering study.
  9. If patient is on NSAIDs, this should be at an unchanged dose for at least 2 weeks before entering study.
  10. Glomerular filtration rate > 60 mls/min/1.73m2.

Exclusion Criteria

  1. Patient known to have the following medical condition(s) will be excluded:

    1. Other autoimmune disease /inflammatory joint disease/connective tissue disease ( e.g. lupus, seronegative spondylarthropathy (e.g. ankylosing spondylitis/psoriatic arthropathy ), reactive arthritis, overlap syndrome, primary sjogren syndrome and mixed connective tissue disease.)
    2. Inflammatory arthritis with onset before 18 years old.
    3. Current or previous history of cancer or lymphoproliferative disease.
    4. HIV positive status, Hepatitis B/C positive status.
    5. Persistent and/or severe infection in the previous 12 weeks.
    6. Major traumatic injury, terminal illness, or other medical condition(s)that could place the patient at risk to participate in the study.
    7. Clinically relevant cardiovascular (e.g unstable ischemic heart disease), neurological (e.g recent stroke), gastroenterology (e.g active peptic ulcer disease), renal (e.g chronic renal failure), hepatic (e.g alcoholic liver disease, fatty liver) and any other major systemic disease that could i) place the patient at risk to participate in the study; or ii) make protocol implementation difficult; or iii) make study results interpretation difficult.
    8. Presence of any known condition(s)/circumstance(s) which would negatively impact compliance or study completion.
  2. Impaired laboratory parameters:

    1. Hemoglobin less than 10.5 g/dl, white blood count less than 4 x 10 (9)/L , platelet count less than 150 x 10(9)/L.
    2. Deranged Liver function test: e.g. elevated AST/ALT.
  3. Wants to consume alcohol while taking the study medications.
  4. Body weight that is less than 45 kg.
  5. Pregnancy/Breastfeeding/Male patient wishing to father children.
  6. Patients with the following medication history will be excluded:

    1. History of Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency.
    2. Known allergy to: i) study medications; or ii) contrast; or iii) drugs whose chemical structures are similar (e.g. sulphonamides, salicylates, etc).
    3. On anticoagulation for any reasons.
    4. Previous treatment (within the last 4 weeks) with: i) oral corticosteroid greater than prednisolone equivalent of 10mg/day; or ii) parenteral/intra-articular corticosteroid injection.
    5. Previous treatment (within the last 12 weeks) with: i) other DMARDs such as sulfasalazine,hydroxychloroquine,chloroquine,gold salts, etc; or ii) investigational drug(s); or iii) other immunosuppressive agents such as cyclophosphamide,cyclosporin,azathioprine and any biologic agents, e.g. anti-TNF.
    6. Previous treatment(any duration) with i) Leflunomide; or ii) Sulfasalazine used together with methotrexate
  7. Contraindication to MRI (e.g. pacemakers, metallic implants/stents, claustrophobia).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Singapore
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01659242
Other Study ID Numbers  ICMJE YK 01-2012
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Singapore General Hospital
Study Sponsor  ICMJE Singapore General Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: York Kiat Tan, MBBS,MRCP Singapore General Hospital
PRS Account Singapore General Hospital
Verification Date November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP